What is the dosage and treatment regimen for Valacyclovir (valacyclovir) in treating herpes simplex virus infections, including genital herpes and cold sores, as well as varicella-zoster virus infections, such as shingles?

Valacyclovir Dosing and Treatment Regimens

Herpes Simplex Virus (HSV) Infections

Genital Herpes - First Episode

For initial genital herpes episodes, valacyclovir 1 gram twice daily for 7-10 days is the recommended treatment, with therapy most effective when initiated within 48 hours of symptom onset. 1

• Treatment may be extended beyond 10 days if healing remains incomplete 1
• Note that 5-30% of first-episode genital herpes cases are caused by HSV-1, though clinical recurrences are much less frequent for HSV-1 than HSV-2 1

Genital Herpes - Recurrent Episodes

For recurrent genital herpes, valacyclovir 500 mg twice daily for 5 days is the CDC-recommended episodic treatment, initiated at the first sign of prodrome or lesions. 2

• Patients should be provided with medication or a prescription in advance to enable immediate treatment initiation 2
• Treatment must be initiated at the first sign of prodrome or genital lesions for maximum efficacy 2
• Alternative dosing: 1 gram once daily for 5 days is equally effective 3

Genital Herpes - Suppressive Therapy

For patients with normal immune function, valacyclovir 1000 mg once daily is recommended for suppressive therapy, reducing recurrence frequency by ≥75%. 2

• For patients with <10 recurrences per year, 500 mg once daily is sufficient 3
• For patients with ≥10 recurrences per year, 1000 mg once daily is more effective 3
• For HIV-infected patients with CD4+ count ≥100 cells/mm³, 500 mg twice daily is recommended 1
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding; transmission can occur even during asymptomatic periods 2

Cold Sores (Herpes Labialis)

For cold sores in patients ≥12 years, valacyclovir 2 grams twice daily for 1 day (two doses taken 12 hours apart) is the recommended treatment. 4

• Therapy should be initiated at the earliest symptom of a cold sore (tingling, itching, or burning) 4
• Treatment should not exceed 1 day (2 doses total) 4

Varicella-Zoster Virus (VZV) Infections

Herpes Zoster (Shingles) - Immunocompetent Patients

For uncomplicated herpes zoster, valacyclovir 1 gram three times daily for 7-10 days is the first-line treatment, continued until all lesions have scabbed. 5

• Treatment is most effective when initiated within 48-72 hours of rash onset 2, 5
• Continue treatment until all lesions have completely scabbed, which is the key clinical endpoint, not an arbitrary 7-day duration 5
• Valacyclovir is significantly more effective than acyclovir in reducing the duration of zoster-associated pain 6

Herpes Zoster - Facial Involvement

For facial herpes zoster, valacyclovir 1 gram three times daily should be initiated immediately due to the risk of ophthalmic and cranial nerve complications. 5

• Treatment urgency is critical given the risk of vision-threatening complications 5
• Continue until all lesions have scabbed 5

Herpes Zoster - Immunocompromised Patients

For immunocompromised patients with herpes zoster (including those on chemotherapy), intravenous acyclovir 5-10 mg/kg every 8 hours is the preferred treatment due to high risk of dissemination. 2, 5

• Oral valacyclovir is inadequate for severely immunocompromised hosts 5
• Continue IV therapy for a minimum of 7-10 days and until clinical resolution 5
• Consider temporary reduction in immunosuppressive medications 5

Chickenpox (Varicella)

For chickenpox in pediatric patients aged 2 to <18 years, valacyclovir 20 mg/kg three times daily for 5 days is recommended, not to exceed 1 gram three times daily. 4

• Therapy should be initiated at the earliest sign or symptom 4

Severe HSV or VZV Disease

Disseminated or Complicated Infections

For any severe HSV or VZV infection with complications (disseminated infection, pneumonitis, hepatitis, or CNS involvement), IV acyclovir 5-10 mg/kg every 8 hours for 5-7 days or until clinical resolution is required instead of oral valacyclovir. 2

• Oral valacyclovir is not appropriate for severe disease requiring hospitalization 2, 1

Special Populations and Considerations

Renal Impairment

Dose adjustments are mandatory for patients with renal impairment to prevent acute renal failure. 4

• CrCl 30-49 mL/min: For herpes zoster, reduce to 1 gram every 12 hours 4
• CrCl 10-29 mL/min: For herpes zoster, reduce to 1 gram every 24 hours 4
• CrCl <10 mL/min: For herpes zoster, reduce to 500 mg every 24 hours 4
• For genital herpes suppression with CrCl 10-29 mL/min, reduce to 500 mg every 24 hours 4
• Hemodialysis patients should receive the recommended dose after hemodialysis 4

High-Dose Therapy Warning

Avoid valacyclovir doses of 8 grams per day in immunocompromised patients due to the risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). 2, 1

• This potentially fatal complication has been reported in immunocompromised patients receiving high-dose prophylactic therapy for prolonged periods 7
• The risk appears higher in patients with advanced HIV disease 7

Acyclovir-Resistant HSV

For acyclovir-resistant HSV, IV foscarnet 40 mg/kg every 8 hours until clinical resolution is the treatment of choice. 2, 1

• All acyclovir-resistant HSV strains are also resistant to valacyclovir 2, 1
• Consider resistance if lesions persist despite appropriate valacyclovir treatment 1

Critical Clinical Pearls

• Timing is everything: Therapy is most effective when initiated within 48 hours of symptom onset for both HSV and VZV; for recurrent HSV, treatment at prodrome provides maximum benefit 2
• Patient counseling: Valacyclovir is not a cure for herpes infections; transmission can occur even during asymptomatic periods and suppressive therapy 2, 4
• Safer sex practices: Patients should be counseled to use safer sex practices in combination with suppressive therapy, as genital herpes is frequently transmitted through asymptomatic viral shedding 4
• Hydration: Patients should maintain adequate hydration during treatment 4
• Monitoring: Monitor renal function closely during therapy, especially with IV acyclovir 5